AstraZeneca’s Combination Treatment for HCC Snags Orphan Drug Designation

AstraZeneca’s Imfinzi (durvalumab) and tremelimumab, an anti-CTLA4 antibody and potential new medicine, were granted Orphan Drug designation by the U.S. Food and Drug Administration as a possible treatment for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer in adults. ¹ HCC represents about 80% of all primary liver cancers. The disease occurs most often in people with chronic liver diseases, such as cirrhosis caused by hepatitis B or hepatitis C infection, according to the Mayo Clinic. The disease is often not discovered until it is more advanced, due, in part, to the lack of symptoms in the early stages. The FDA grants Orphan Drug designation for medications intended to treat diseases that affect fewer than 200,000 people in the United States. Liver cancer is the third leading cause of cancer death worldwide. For patients with unresectable or advanced disease state, only 13% are alive five years after diagnosis, AstraZeneca said.

The combination of Imfinzi and tremelimumab is being studied as a treatment for HCC in the Phase III HIMALAYA trial. The trial is also assessing Imfinzi as a stand-alone treatment for HCC. The drugs are being assessed against the standard-of-care medicine Nexavar (sorafenib), a multi-kinase inhibitor, in patients with unresectable, advanced HCC who have not been treated with prior systemic therapy and are not eligible for locoregional therapy. The primary endpoint is overall survival and key secondary endpoints include objective response rate and progression-free survival. HIMALAYA is the first trial to test dual immune checkpoint blockade in the 1st-line advanced HCC setting.

“Many patients with liver cancer are diagnosed and treated only after the disease is advanced, and there is an urgent need for new effective and tolerable treatments. We are eager to bring new potential options to these patients and look forward to the results of our ongoing Phase III HIMALAYA trial later this year,” José Baselga, AstraZeneca’s head of oncology research and development said in a statement.

Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80. Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation and boosting the immune response to cancer. Last year, the combination of Imfinzi and tremelimumab did not meet the primary endpoint of improving overall survival compared to standard-of-care chemotherapy in previously-untreated Stage IV non-small cell lung cancer.

In October, the combination posted a win with positive progression-free survival results for Imfinzi and tremelimumab from the Phase III POSEIDON trial in previously-untreated Stage IV (metastatic) non-small cell lung cancer.

Additionally, tremelimumab is being tested in combination with Imfinzi in bladder cancer, head and neck cancer, liver cancer and blood cancers.